This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Topical microbicides represent an important potential strategy for preventing the transmission of HIV/STD. It is desirable that a topical microbicide product be effective in preventing HIV and STD infections while not irritating the mucosal surface or adversely affecting normal flora of the vagina or rectum, after single and repeated use. It is essential that the in vivo activity of developing topical microbicidal products be evaluated prior to recommendations for widespread intravaginal or rectal use. Because clinical trials are too cumbersome and expensive for screening purposes, animal models need to be used. The primary goal of this study is to develop a combination topical microbicide product. That is to say, a product which will be composed of more than one active (antimicrobial) compound, providing more than one mode of action against HIV and other STI. As the proposed combination topical microbicide formulation evolves, we will assess safety of intermediary formulated products in the rectal and vaginal environments using our established animal model for topical microbicide safety testing. These proposed studies are key to bridging the gap between laboratory and clinical studies aimed at preventing the spread of HIV/STI.